Suppression of erythromycin-induced early afterdepolarizations and torsade de pointes ventricular tachycardia by mexiletine.
Erythromycin is a selective IKr-blocking, action potential duration (APD)-prolonging drug, which may induce early afterdepolarizations (EADs) and torsade de pointes ventricular tachycardia. The successful termination of an erythromycin-induced clinical torsades de pointes by the authors with mexiletine prompted them to investigate in vitro whether erythromycin is able to induce EADs in Purkinje fibers and, if so, whether EADs are suppressible or not by mexiletine. Electrically stimulated canine Purkinje fibers (n = 9) were superfused with erythromycin (200 mg/l) and action potentials were recorded by an intracellular microelectrode technique. Erythromycin induced a pronounced prolongation of APD and the appearance of EADs in all Purkinje preparations (9/9). After the addition of mexiletine (10 mM), a marked shortening of APD and the disappearance of EADs (7/9) were observed. Mexiletine, an inhibitor of the tetrodotoxin-sensitive window Na(+)-current, may prevent IKr-blocking drug-induced torsade de pointes ventricular tachycardia by abolishing APD prolongation and EADs.
Fazekas
T
T
Department of Cardiology, Békés County Hospital, Gyula, Hungary.
Krassói
I
I
Lengyel
C
C
Varró
A
A
Papp
J G
JG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004558:Electric Stimulation; D004917:Erythromycin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008801:Mexiletine / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011690:Purkinje Fibers / Q000187:drug effects*; D013575:Syncope / Q000139:chemically induced; D016171:Torsades de Pointes / Q000139:chemically induced / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D008801:Mexiletine; D004917:Erythromycin